This phase I trial is studying the side effects and best dose of bortezomib in treating young patients with refractory or recurrent leukemia. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.
OBJECTIVES: Primary I. Determine the maximum tolerated dose and recommended phase II dose of bortezomib in children with refractory or recurrent leukemia. II. Determine the toxic effects of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients. Secondary I. Determine, preliminarily, the antitumor activity of this drug in these patients. II. Determine, preliminarily, the biologic activity of this drug in these patients. OUTLINE: This is a dose-escalation, open-label, multicenter study. Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 1.5-36 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
COG Phase I Consortium
Arcadia, California, United States
Maximum tolerated dose and recommended phase II dose
Time frame: Up to 21 days
Toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 3.0
Time frame: Up to 2 years
Pharmacokinetics as assessed by confidence intervals (CI), area under the curve (AUC), and half-life (T ½)
Time frame: Pretreatment, days 1, 8, 18-22 of course 1
Antitumor activity
Time frame: Up to 2 years
Correlate apoptosis and NF-kB activation
Time frame: Prestudy, days 8 and 18
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